1. Field of Invention
The inventive subject matter relates to DNA sequences and polypeptides from Plasmodium falciparum for use as an anti-malaria vaccine component and methods of inducing an immune response to these antigens.
2. Background Art
Malaria is caused by the vector borne organism Plasmodium spp. The parasite has a complex lifecycle requiring stage specific expression of proteins. These proteins can be expressed at different stages or be specific to stages. Malaria is an extremely important disease, with over 3 billion people living in malaria endemic areas. Over 1 million deaths are attributable to malaria per year. The emergence of drug resistant strains has compounded the problem of treating the disease. Unfortunately, no FDA-approved vaccine exists.
The entire genomic sequence of P. falciparum has been sequenced (Bowman et al., Nature, 400: 532-538 (1999), Gardner, et al., Nature, 419: 498-511 (2002)). The rodent malaria parasite, P. yoelii has also been sequenced (Carlton et al., Nature, 419: 512-519 (2002)). Despite this, however, the development of efficacious anti-malaria vaccines has been severely hampered by the paucity of promising antigens. Sequencing of the Plasmodium falciparum and Plasmodium yoelii genomes yielding identification over 5,200 genes in the genome. However, despite the large number of potential gene targets, use of the data set alone will not likely result in new vaccine constructs. Consequently, only 0.2% of the P. falciparum proteome is undergoing clinical testing. Moreover, these vaccine candidate antigens have failed to induce significant protection in volunteers. Nevertheless, immunization of mice and humans with radiation-attenuated sporozoites results in a high-grade immunity (>90%), suggesting that development of effective anti-malaria vaccines are possible. This protective immunity appears to target multiple sporozoite and liver stage antigens.